Antibacterial compounds

ABSTRACT

Bacterial protein synthesis-inhibiting compounds having formula (I)  
                 
and salts, prodrugs, salts of prodrugs, and metabolites thereof, processes for making the compounds and intermediates in the processes, compositions containing the compounds, and methods of using the compounds are disclosed.

This application claims the benefit of U.S. Provisional Application No.60/542,307, filed Feb. 6, 2004.

FIELD OF THE INVENTION

This invention pertains to compounds which inhibit bacterial proteinsynthesis, processes for making the compounds and intermediates in theprocesses, compositions containing the compounds, and uses for thecompounds.

BACKGROUND OF THE INVENTION

Because the effectiveness of many drugs currently available for treatingbacterial infections can be compromised by the emergence ofdrug-resistant bacteria, novel antibacterials would be useful for theirtherapeutic value and their contribution to the antibacterial arts.

SUMMARY OF THE INVENTION

Accordingly, one embodiment of this invention pertains to compounds, andsalts, prodrugs, salts of prodrugs, and metabolites thereof, whichinhibit bacterial protein synthesis, the compounds having formula (I)

in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or —N(R⁷)₂; R² is hydrogen orR^(P), in which R^(P) is —C(CH₃)₃, —O(CH₂CH═CH₂), or(2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸, —C(O)R⁸, —C(O)OR⁸, R⁹,—C(O)OCH₂R⁹, or R¹⁰; R⁴ is hydrogen, R¹¹, —C(O)R¹¹, R¹², R¹³, R¹⁴, orR¹⁵; R⁵ is hydrogen, R¹⁶, —C(O)R¹⁶, R¹⁷, R¹⁸, R¹⁹, or R²⁰; R⁶ ishydrogen, R²¹, —OH, —OR²¹, —NH₂, —NHR²¹, —N(R²¹)₂; R⁷ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁸ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(8a); R^(8a) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(8b), —NH₂, —NHR^(8b),—N(R^(8b))₂, or R^(8c) substituents; R^(8b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(8c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(8d), —F, —Cl, —Br, —I, —OH, —OR^(8d), —NO₂, —NH₂, —NHR^(8d),or —N(R^(8d))₂ substituents; R^(8d) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁹ is phenyl which is unfused or fusedwith benzene, cyclopentane, cyclopentene, cyclohexane, or cyclohexene,in which each ring is independently unsubstituted or substituted withone or two or three independently selected R^(9a), —F, —Cl, —Br, —I,—OH, —OR^(9a), —NO₂, —NH₂, —NHR^(9a), or —N(R^(9a))₂ substituents;R^(9a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl;R¹⁰ is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(10a), —F, —Cl, —Br, —I, —OH, —OR^(10a), —NO₂, —NH₂,—NHR^(10a), or —N(R^(10a))₂ substituents; R^(10a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(11a); R^(11a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b), —NH₂, —NHR^(11b), N(R^(11b))₂,or R^(11c) substituents; R^(11b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(11c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(11d), —F,—Cl, —Br, —I, —OH, —OR^(11d), —NO₂, —NH₂, —NHR^(11d), or —N(R^(11d))₂substituents; R^(11d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹² is C₂-alkenyl, C₃-alkenyl, C₄-alkenyl,C₅-alkenyl, C₆-alkenyl, or R^(12a); R^(12a) is C₂-alkenyl, C₃-alkenyl,C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(12b), —NH₂, —NHR^(12b), —N(R^(12b))₂, or R^(12c)substituents; R^(12b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(12c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(12d), —F,—Cl, —Br, —I, —OH, —OR^(12d), —NO₂, —NH₂, —NHR^(12d), or —N(R^(12d))₂substituents; R^(12d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹³ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(13a); R^(13a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(13b), —NH₂, —NHR^(13b), —N(R^(13b))₂, or R^(13c)substituents; R^(13b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(13c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(13d), —F,—Cl, —Br, —I, —OH, —OR^(13d), —NO₂, —NH₂, —NHR^(13d), or —N(R^(13d))₂substituents; R^(13d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁴ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(14a); R^(14a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(14b), —NH₂, —NHR^(14b), —N(R^(14b))₂, or R^(14c)substituents; R^(14b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(14c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(14d), —F,—Cl, —Br, —I, —OH, —OR^(14d), —NO₂, —NH₂, —NHR^(14d), or —N(R^(14d))₂substituents; R^(14d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁵ is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unfused or fused with benzene, furan,imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, oxazole, pyrazine,pyrazole, pyridazine, pyridine, pyrrole, thiazole, or thiophene, inwhich each ring is independently unsubstituted or substituted with oneor two or three independently selected R^(15a), —F, —Cl, —Br, —I, —OH,—OR^(15a), —NO₂, —NH₂, —NHR^(15a), or —N(R^(15a))₂ substituents; R^(15a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁶ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(16a);R^(16a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b), —NH₂,—NHR^(11b), —N(R^(11b))₂, or R^(16c) substituents; R^(16b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(6c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(16d), —F, —Cl, —Br, —I, —OH, —OR^(16d), —NO₂, —NH₂,—NHR^(16d), or —N(R^(16d))₂ substituents; R^(16d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁷ is C₂-alkenyl,C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, or R^(17a); R^(17a) isC₂-alkenyl, C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(17b) —NH₂, —NHR^(17b),—N(R^(17b))₂, or R^(17c) substituents; R^(17b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(17c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(17d), —F, —Cl, —Br, —I, —OH, OR^(17d), —NO₂, —NH₂,—NHR^(17d), or —N(R^(17d))₂ substituents; R^(17d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁸ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(18a); R^(18a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(18b), —NH₂, NHR^(18b),—N(R^(18b))₂, or R^(18c) substituents; R^(18b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(18c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(18d), —F, —Cl, —Br, —I, —OH, —OR^(18d), —NO₂, —NH₂,—NHR^(18d), or —N(R^(18d))₂ substituents; R^(18d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁹ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(19a); R^(19a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(19b), —NH₂, —NHR^(19b),—N(R^(19b))₂, or R^(19c) substituents; R^(19b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(19c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(19d), —F, —Cl, —Br, —I, —OH, —OR^(19d), —NO₂, —NH₂,—NHR^(19d), or —N(R^(19d))₂ substituents; R^(19d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁰ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(20a), —F, —Cl, —Br, —I, —OH, —OR^(20a), —NO₂, —NH₂,—NHR^(20a), or —N(R^(20a))₂ substituents; R^(20a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(21a); R^(21a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(21b), —NH₂, —NHR^(21b), —N(R^(21b))₂,or R^(21b) substituents; R^(21b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(21c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(21d), —F,—Cl, —Br, —I, —OH, —OR^(21d), —NO₂, —NH₂, —NHR^(21d), or —N(R^(21d))₂substituents; R^(21d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; X¹ is —O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—;R²² is R²³, —OH, —OR²³, —C(O)R²³, —C(O)OR²³, —C(O)OCH₂R²⁴, —R²⁵, or—CH₂R²⁵R²³ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl,C₆-alkyl, or R^(23a); R^(23a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, C₆-alkyl, each of which is substituted with one or two orthree independently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH,—OR^(23b), —NH₂, —NHR^(23b), —N(R^(23b))₂, or R^(23c) substituents;R^(23b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl; R^(23c) is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unfused or fused with benzene, furan,imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, oxazole, pyrazine,pyrazole, pyridazine, pyridine, pyrrole, thiazole, or thiophene, inwhich each ring is independently unsubstituted or substituted with oneor two or three independently selected R^(23d), —F, —Cl, —Br, —I, —OH,—OR^(23d), —NO₂, —NH₂, —NHR^(23d), or —N(R^(23d))₂ substituents; R^(23d)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁴ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(24a);R^(24a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(24b), —NH₂,—NHR^(24b), —N(R^(24b))₂, or R^(24c) substituents; R^(24b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(24c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(24d), —F, —Cl, —Br, —I, —OH, —OR^(24d), —NO₂, —NH₂,—NHR^(24d), or —N(R^(24d))₂ substituents; R^(24d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; and R²⁵ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(25a), —F, —Cl, —Br, —I, —OH, —OR^(25a), —NO₂, —NH₂,—NHR^(25a), or —N(R^(25a))₂ substituents; R^(25a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl.

Another embodiment of this invention pertains to processes for makingthe compounds of this invention having formula (I), and salts, prodrugs,salts of prodrugs, and metabolites thereof.

Still another embodiment of this invention pertains to intermediateswhich are used in the processes for making the compounds of thisinvention having formula (I), and salts, prodrugs, salts of prodrugs,and metabolites thereof.

Still yet another embodiment of this invention pertains to metabolitesof the compounds of this invention having formula (I), and salts,prodrugs, salts of prodrugs, and metabolites thereof.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial protein synthesis in an in vitroenvironment, the compositions comprising a therapeutically effectiveamount of a compound of this invention having formula (I), or a salt,prodrug, salt of a prodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial protein synthesis in an in vitroenvironment, the compositions comprising therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial proteinsynthesis in an in vitro environment, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial proteinsynthesis in an in vitro environment, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial proteinsynthesis in an in vitro environment, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial proteinsynthesis in an in vitro environment, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free bacterial protein synthesis in anin vitro environment, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free bacterial protein synthesis in anin vitro environment, the compositions comprising therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, antibacterial-resistant bacterialprotein synthesis in an in vitro environment, the compositionscomprising a therapeutically effective amount of a compound of thisinvention having formula (I), or a salt, prodrug, salt of a prodrug, ormetabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, antibacterial-resistant bacterialprotein synthesis in an in vitro environment, the compositionscomprising more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, quinolone-resistant bacterialprotein synthesis in an in vitro environment, the compositionscomprising a therapeutically effective amount of a compound of thisinvention having formula (I), or a salt, prodrug, salt of a prodrug, ormetabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, quinolone-resistant bacterialprotein synthesis in an in vitro environment, the compositionscomprising therapeutically effective amounts of more than one compoundof this invention having formula (I), or salts, prodrugs, salts ofprodrugs, or metabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial growth in an in vitro environment,the compositions comprising a therapeutically effective amount of acompound of this invention having formula (I), or a salt, prodrug, saltof a prodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial growth in an in vitro environment,the compositions comprising therapeutically effective amounts of morethan one compound of this invention having formula (I), or salts,prodrugs, salts of prodrugs, or metabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial growth inan in vitro environment, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial growth inan in vitro environment, the compositions comprising therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial growth in anin vitro environment, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial growth in anin vitro environment, the compositions comprising therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free bacterial growth in an in vitroenvironment, the compositions comprising a therapeutically effectiveamount of a compound of this invention having formula (I), or a salt,prodrug, salt of a prodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free bacterial growth in an in vitroenvironment, the compositions comprising therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, antibacterial-resistant bacterialgrowth in an in vitro environment, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, antibacterial-resistant bacterialgrowth in an in vitro environment, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, quinolone-resistant bacterialgrowth in an in vitro environment, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting cell-free, quinolone-resistant bacterialgrowth in an in vitro environment, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial protein synthesis in a fish or amammal, the compositions comprising a therapeutically effective amountof a compound of this invention having formula (I), or a salt, prodrug,salt of a prodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial protein synthesis in a fish or amammal, the compositions comprising therapeutically effective amounts ofmore than one compound of this invention having formula (I), or salts,prodrugs, salts of prodrugs, or metabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial proteinsynthesis in a fish or a mammal, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial proteinsynthesis in a fish or a mammal, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial proteinsynthesis in a fish or a mammal, the compositions comprising atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial proteinsynthesis in a fish or a mammal, the compositions comprisingtherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial growth in a fish or a mammal, thecompositions comprising a therapeutically effective amount of a compoundof this invention having formula (I), or a salt, prodrug, salt of aprodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting bacterial growth in a fish or a mammal, thecompositions comprising therapeutically effective amounts of more thanone compound of this invention having formula (I), or salts, prodrugs,salts of prodrugs, or metabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial growth ina fish or a mammal, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting antibacterial-resistant bacterial growth ina fish or a mammal, the compositions comprising therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial growth in afish or a mammal, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for inhibiting quinolone-resistant bacterial growth in afish or a mammal, the compositions comprising therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for treating bacterial infections in a fish or a mammal,the compositions comprising a therapeutically effective amount of acompound of this invention having formula (I), or a salt, prodrug, saltof a prodrug, or metabolite thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for treating bacterial infections in a fish or a mammal,the compositions comprising therapeutically effective amounts of morethan one compound of this invention having formula (I), or salts,prodrugs, salts of prodrugs, or metabolites thereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for treating antibacterial-resistant bacterial infectionsin a fish or a mammal, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for treating antibacterial-resistant bacterial infectionsin a fish or a mammal, the compositions comprising therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof, and an excipient.

Still even yet another embodiment of this invention pertains tocompositions for treating quinolone-resistant bacterial infections in afish or a mammal, the compositions comprising a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof, and anexcipient.

Still even yet another embodiment of this invention pertains tocompositions for treating quinolone-resistant bacterial infections in afish or a mammal, the compositions comprising therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof, and anexcipient.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial protein synthesis in an in vitro environment,the methods comprising administering thereto a therapeutically effectiveamount of a compound of this invention having formula (I), or a salt,prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial protein synthesis in an in vitro environment,the methods comprising administering thereto therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial protein synthesis an inan in vitro environment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial protein synthesis in anin vitro environment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial protein synthesis in an invitro environment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial protein synthesis in an invitro environment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free bacterial protein synthesis in an in vitroenvironment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free bacterial protein synthesis in an in vitroenvironment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, antibacterial-resistant bacterial proteinsynthesis in an in vitro environment, the methods comprisingadministering thereto a therapeutically effective amount of a compoundof this invention having formula (I), or salt, prodrug, salt of aprodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, antibacterial-resistant bacterial proteinsynthesis in an in vitro environment, the methods comprisingadministering thereto therapeutically effective amounts of more than onecompound of this invention having formula (I), or salts, prodrugs, saltsof prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, quinolone-resistant bacterial proteinsynthesis in an in vitro environment, the methods comprisingadministering thereto a therapeutically effective amount of a compoundof this invention having formula (I), or a salt, prodrug, salt of aprodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, quinolone-resistant bacterial proteinsynthesis in an in vitro environment, the methods comprisingadministering thereto therapeutically effective amounts of more than onecompound of this invention having formula (I), or salts, prodrugs, saltsof prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial growth in an in vitro environment, the methodscomprising administering thereto a therapeutically effective amount of acompound of this invention having formula (I), or a salt, prodrug, saltof a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial growth in an in vitro environment, the methodscomprising administering thereto therapeutically effective amounts ofmore than one compound of this invention having formula (I), or salts,prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial growth in an in vitroenvironment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial growth in an in vitroenvironment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial growth in an in vitroenvironment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial growth in an in vitroenvironment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free bacterial growth in an in vitro environment,the methods comprising administering thereto a therapeutically effectiveamount of a compound of this invention having formula (I), or a salt,prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free bacterial growth in an in vitro environment,the methods comprising administering thereto therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, antibacterial-resistant bacterial growth in anin vitro environment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, antibacterial-resistant bacterial growth in anin vitro environment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, quinolone-resistant bacterial growth in an invitro environment, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting cell-free, quinolone-resistant bacterial growth in an invitro environment, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial protein synthesis in a fish or a mammal, themethods comprising administering thereto a therapeutically effectiveamount of a compound of this invention having formula (I), or a salt,prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial protein synthesis in a fish or a mammal, themethods comprising administering thereto therapeutically effectiveamounts of more than one compound of this invention having formula (I),or salts, prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial protein synthesis in afish or a mammal, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial protein synthesis in afish or a mammal, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial protein synthesis in a fishor a mammal, the methods comprising administering thereto atherapeutically effective amount of a compound of this invention havingformula (I), or a salt, prodrug, salt of a prodrug, or metabolitethereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial protein synthesis in a fishor a mammal, the methods comprising administering theretotherapeutically effective amounts of more than one compound of thisinvention having formula (I), or salts, prodrugs, salts of prodrugs, ormetabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial growth in a fish or a mammal, the methodscomprising administering thereto a therapeutically effective amount of acompound of this invention having formula (I), or a salt, prodrug, saltof a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting bacterial growth in a fish or a mammal, the methodscomprising administering thereto therapeutically effective amounts ofmore than one compound of this invention having formula (I), salts,prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial growth in a fish or amammal, the methods comprising administering thereto a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting antibacterial-resistant bacterial growth in a fish or amammal, the methods comprising administering thereto therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial growth in a fish or amammal, the methods comprising administering thereto a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor inhibiting quinolone-resistant bacterial growth in a fish or amammal, the methods comprising administering thereto therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof.

Still even yet another embodiment of this invention pertains to methodsfor treating bacterial infections in a fish or a mammal, the methodscomprising administering thereto a therapeutically effective amount of acompound of this invention having formula (I), or a salt, prodrug, saltof a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor treating bacterial infections in a fish or a mammal, the methodscomprising administering thereto therapeutically effective amounts ofmore than one compound of this invention having formula (I), or salts,prodrugs, salts of prodrugs, or metabolites thereof.

Still even yet another embodiment of this invention pertains to methodsfor treating antibacterial-resistant bacterial infections in a fish or amammal, the methods comprising administering thereto a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor treating antibacterial-resistant bacterial infections in a fish or amammal, the methods comprising administering thereto therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof.

Still even yet another embodiment of this invention pertains to methodsfor treating quinolone-resistant bacterial infections in a fish or amammal, the methods comprising administering thereto a therapeuticallyeffective amount of a compound of this invention having formula (I), ora salt, prodrug, salt of a prodrug, or metabolite thereof.

Still even yet another embodiment of this invention pertains to methodsfor treating quinolone-resistant bacterial infections in a fish or amammal, the methods comprising administering thereto therapeuticallyeffective amounts of more than one compound of this invention havingformula (I), or salts, prodrugs, salts of prodrugs, or metabolitesthereof.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of this invention are represented by fixed and variablemoieties, the latter of which are represented by identifiers (capitalletters with numerical and/or alphabetical superscripts) and can bespecifically embodied. It is meant to be understood that a specificembodiment of a variable moiety can be the same or different as anotherspecific embodiment having the same identifier if the possibility ofmore than one specific embodiment having that identifier exists.

The term “C₂-alkenyl” means ethenyl(vinyl).

The term “C₃-alkenyl” means 1-propen-1-yl, 1-propen-2-yl(isopropenyl),and 1-propen-3-yl(allyl).

The term “C₄-alkenyl” means 1-buten-1-yl, 1-buten-2-yl,1,3-butadien-1-yl, 1,3-butadien-2-yl, 2-buten-1-yl, 2-buten-2-yl,3-buten-1-yl, 3-buten-2-yl, 2-methyl-1-propen-1-yl, and2-methyl-2-propen-1-yl.

The term “C₅-alkenyl” means 2-methylene-3-buten-1-yl,2-methylenebut-1-yl, 2-methyl-1-buten-1-yl, 2-methyl-1,3-butadien-1-yl,2-methyl-2-buten-1-yl, 2-methyl-3-buten-1-yl, 2-methyl-3-buten-2-yl,3-methyl-1-buten-1-yl, 3-methyl-1-buten-2-yl,3-methyl-1,3-butadien-1-yl, 3-methyl-1,3-butadien-2-yl,3-methyl-2-buten-1-yl, 3-methyl-2-buten-2-yl, 3-methyl-3-buten-1-yl,3-methyl-3-buten-2-yl, 1-penten-1-yl, 1-penten-2-yl, 1-penten-3-yl,1,3-pentadien-1-yl, 1,3-pentadien-2-yl, 1,3-pentadien-3-yl,1,4-pentadien-1-yl, 1,4-pentadien-2-yl, 1,4-pentadien-3-yl,2-penten-1-yl, 2-penten-2-yl, 2-penten-3-yl, 2,4-pentadien-1-yl,2,4-pentadien-2-yl, 3-penten-1-yl, 3-penten-2-yl, 4-penten-1-yl, and4-penten-2-yl.

The term “C₆-alkenyl” means 2,2-dimethyl-3-buten-1-yl,2,3-dimethyl-1-buten-1-yl, 2,3-dimethyl-1,3-butadien-1-yl,2,3-dimethyl-2-buten-1-yl, 2,3-dimethyl-3-buten-1-yl,2,3-dimethyl-3-buten-2-yl, 3,3-dimethyl-1-buten-1-yl,3,3-dimethyl-1-buten-2-yl, 2-ethenyl-1,3-butadien-1-yl,2-ethenyl-2-buten-1-yl, 2-ethyl-1-buten-1-yl, 2-ethyl-1,3-butadien-1-yl,2-ethyl-2-buten-1-yl, 2-ethyl-3-buten-1-yl, 1-hexen-1-yl, 1-hexen-2-yl,1-hexen-3-yl, 1,3-hexadien-1-yl, 1,3-hexadien-2-yl, 1,3-hexadien-3-yl,1,3,5-hexatrien-1-yl, 1,3,5-hexatrien-2-yl, 1,3,5-hexatrien-3-yl,1,4-hexadien-1-yl, 1,4-hexadien-2-yl, 1,4-hexadien-3-yl,1,5-hexadien-1-yl, 1,5-hexadien-2-yl, 1,5-hexadien-3-yl, 2-hexen-1-yl,2-hexen-2-yl, 2-hexen-3-yl, 2,4-hexadien-1-yl, 2,4-hexadien-2-yl,2,4-hexadien-3-yl, 2,5-hexadien-1-yl, 2,5-hexadien-2-yl,2,5-hexadien-3-yl, 3-hexen-1-yl, 3-hexen-2-yl, 3-hexen-3-yl,3,5-hexadien-1-yl, 3,5-hexadien-2-yl, 3,5-hexadien-3-yl, 4-hexen-1-yl,4-hexen-2-yl, 4-hexen-3-yl, 5-hexen-1-yl, 5-hexen-2-yl, 5-hexen-3-yl,2-methylene-3-methyl-3-buten-1-yl, 2-methylene-3-methylbut-1-yl,2-methylene-3-penten-1-yl, 2-methylene-4-penten-1-yl,2-methylenepent-1-yl, 2-methylenepent-3-yl, 3-methylene-1-penten-1-yl,3-methylene-1-penten-2-yl, 3-methylenepent-1-yl,3-methylene-1,4-pentadien-1-yl, 3-methylene-1,4-pentadien-2-yl,3-methylenepent-2-yl, 2-methyl-1-penten-1-yl, 2-methyl-1-penten-3-yl,2-methyl-1,3-pentadien-1-yl, 2-methyl-1,3-pentadien-3-yl,2-methyl-1,4-pentadien-1-yl, 2-methyl-1,4-pentadien-3-yl,2-methyl-2-penten-1-yl, 2-methyl-2-penten-3-yl,2-methyl-2,4-pentadien-1-yl, 2-methyl-2,4-pentadien-3-yl,2-methyl-3-penten-1-yl, 2-methyl-3-penten-2-yl, 2-methyl-3-penten-3-yl,2-methyl-4-penten-1-yl, 2-methyl-4-penten-2-yl, 2-methyl-4-penten-3-yl,3-methyl-1-penten-1-yl, 3-methyl-1-penten-2-yl,3-methyl-1,3-pentadien-1-yl, 3-methyl-1,3-pentadien-2-yl,3-methyl-1,4-pentadien-1-yl, 3-methyl-1,4-pentadien-2-yl,3-methyl-2-penten-1-yl, 3-methyl-2-penten-2-yl,3-methyl-2,4-pentadien-1-yl, 3-methyl-3-penten-1-yl,3-methyl-3-penten-2-yl, 3-methyl-4-penten-1-yl, 3-methyl-4-penten-2-yl,3-methyl-4-penten-3-yl, 4-methyl-1-penten-1-yl, 4-methyl-1-penten-2-yl,4-methyl-1-penten-3-yl, 4-methyl-1,3-pentadien-1-yl,4-methyl-1,3-pentadien-2-yl, 4-methyl-1,3-pentadien-3-yl,4-methyl-1,4-pentadien-1-yl, 4-methyl-1,4-pentadien-2-yl,4-methyl-1,4-pentadien-3-yl, 4-methylene-2-penten-3-yl,4-methyl-2-penten-1-yl, 4-methyl-2-penten-2-yl, 4-methyl-2-penten-3-yl,4-methyl-2,4-pentadien-1-yl, 4-methyl-2,4-pentadien-2-yl,4-methyl-3-penten-1-yl, 4-methyl-3-penten-2-yl, 4-methyl-3-penten-3-yl,4-methyl-4-penten-1-yl, and 4-methyl-4-penten-2-yl.

The term “C₁-alkyl” means methyl.

The term “C₂-alkyl” means ethyl.

The term “C₃-alkyl” means prop-1-yl and prop-2-yl (isopropyl)

The term “C₄-alkyl” means but-1-yl, but-2-yl, 2-methylprop-1-yl, and2-methylprop-2-yl(tert-butyl).

The term “C₅-alkyl” means 2,2-dimethylprop-1-yl (neo-pentyl),2-methylbut-1-yl, 2-methylbut-2-yl, 3-methylbut-1-yl, 3-methylbut-2-yl,pent-1-yl, pent-2-yl, and pent-3-yl.

The term “C₆-alkyl” means 2,2-dimethylbut-1-yl, 2,3-dimethylbut-1-yl,2,3-dimethylbut-2-yl, 3,3-dimethylbut-1-yl, 3,3-dimethylbut-2-yl,2-ethylbut-1-yl, hex-1-yl, hex-2-yl, hex-3-yl, 2-methylpent-1-yl,2-methylpent-2-yl, 2-methylpent-3-yl, 3-methylpent-1-yl,3-methylpent-2-yl, 3-methylpent-3-yl, 4-methylpent-1-yl, and4-methylpent-2-yl.

The term “C₂-alkynyl” means ethynyl(acetylenyl).

The term “C₃-alkynyl” means 1-propyn-1-yl and 2-propyn-1-yl(propargyl).

The term “C₄-alkynyl” means 1-butyn-1-yl, 1,3-butadiyn-1-yl,2-butyn-1-yl, 3-butyn-1-yl, and 3-butyn-2-yl.

The term “C₅-alkynyl” means 2-methyl-3-butyn-1-yl,2-methyl-3-butyn-2-yl, 3-methyl-1-butyn-1-yl, 1,3-pentadiyn-1-yl,1,4-pentadiyn-1-yl, 1,4-pentadiyn-3-yl, 2,4-pentadiyn-1-yl,1-pentyn-1-yl, 1-pentyn-3-yl, 2-pentyn-1-yl, 3-pentyn-1-yl,3-pentyn-2-yl, 4-pentyn-1-yl, and 4-pentyn-2-yl.

The term “C₆-alkynyl” means 2,2-dimethyl-3-butyn-1-yl,3,3-dimethyl-1-butyn-1-yl, 2-ethyl-3-butyn-1-yl, 2-ethynyl-3-butyn-1-yl,1-hexyn-1-yl, 1-hexyn-3-yl, 1,3-hexadiyn-1-yl, 1,3,5-hexatriyn-1-yl,1,4-hexadiyn-1-yl, 1,4-hexadiyn-3-yl, 1,5-hexadiyn-1-yl,1,5-hexadiyn-3-yl, 2-hexyn-1-yl, 2,5-hexadiyn-1-yl, 3-hexyn-1-yl,3-hexyn-2-yl, 3,5-hexadiyn-2-yl, 4-hexyn-1-yl, 4-hexyn-2-yl,4-hexyn-3-yl, 5-hexyn-1-yl, 5-hexyn-2-yl, 5-hexyn-3-yl,2-methyl-3-pentyn-1-yl, 2-methyl-3-pentyn-2-yl, 2-methyl-4-pentyn-1-yl,2-methyl-4-pentyn-2-yl, 2-methyl-4-pentyn-3-yl, 3-methyl-1-pentyn-1-yl,3-methyl-4-pentyn-1-yl, 3-methyl-4-pentyn-2-yl,3-methyl-1,4-pentadiyn-1-yl, 3-methyl-1,4-pentadiyn-3-yl,3-methyl-4-pentyn-1-yl, 3-methyl-4-pentyn-3-yl, 4-methyl-1-pentyn-1-yl,and 4-methyl-2-pentyn-1-yl.

Variable moieties can combine with the parent molecular moieties of thecompounds of this invention to provide still even yet another embodimentof this invention, which embodiment pertains to compounds of thisinvention having formula (I), and salts, prodrugs, salts of prodrugs,and metabolites thereof, in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or—N(R⁷)₂; R² is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃,—O(CH₂CH═CH₂), or (2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸,—C(O)R⁸, —C(O)OR⁸, R⁹, —C(O)OCH₂R⁹, or R¹⁰; R⁴ is hydrogen, R¹¹,—C(O)R¹¹, R¹², R¹³, R¹⁴, or R¹⁵; R⁵ is hydrogen, R¹⁶, —C(O)R¹⁶, R¹⁷,R¹⁸, or R¹⁹, R²⁰; R⁶ is hydrogen, R²¹, —OH, —OR²¹, —NH₂, —NHR²¹,—N(R²¹)₂; R⁷ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl; R⁸ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl,C₆-alkyl, or R^(8a); R^(8a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, C₆-alkyl, each of which is substituted with one or two orthree independently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH,—OR^(8b), —NH₂, —NHR^(8b), —N(R^(8b))₂, or R^(8c) substituents; R^(8b)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(8c)is phenyl, furanyl, imidazolyl, isothiazolyl, isoxazolyl,1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(8d), —F, —Cl, —Br, —I, —OH,—OR^(8d), —NO₂, —NH₂, —NHR^(8d), or —N(R^(8d))₂ substituents; R^(8d) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁹ isphenyl which is unsubstituted or substituted with one or two or threeindependently selected R^(9a), —F, —Cl, —Br, —I, —OH, —OR^(9a), —NO₂,—NH₂, —NHR^(9a), or —N(R^(9a))₂ substituents; R^(9a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁰ is furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(10a), —F, —Cl, —Br, —I, —OH, —OR^(10a), —NO₂, —NH₂,—NHR^(10a), or —N(R^(10a))₂ substituents; R^(10a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(11a); R^(11a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b)—NH₂, —NHR^(11b), —N(R^(11b))₂, orR^(11c) substituents; R^(11b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(11c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(11d), —F,—Cl, —Br, —I, —OH, —OR^(11d), —NO₂, —NH₂, —NHR^(11d), or —N(R^(11d))₂substituents; R^(11d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹² is C₂-alkenyl, C₃-alkenyl, C₄-alkenyl,C₅-alkenyl, C₆-alkenyl, or R^(12a); R^(12a) is C₂-alkenyl, C₃-alkenyl,C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃ , —CF₂CF₃, —OH, —OR^(12b), —NH₂, —NHR^(12b), —N(R^(12b))₂, or R^(12c)substituents; R^(12b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(12c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(12d), —F,—Cl, —Br, —I, —OH, —OR^(12d), —NO₂, —NH₂, —NHR^(12d), or —N(R^(12d))₂substituents; R^(12d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹³ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(13a); R^(13a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(13b), —NH₂, —NHR^(13b), —N(R^(13b))₂, or R^(13c)substituents; R^(13b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(13c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(13d), —F,—Cl, —Br, —I, —OH, —OR^(13d), —NO₂, —NH₂, —NHR^(13d), or —N(R¹³)₂substituents; R^(13d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁴ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(14a); R^(14a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(14b), —NH₂, —NHR^(14b), —N(R^(14b))₂, or R^(14c)substituents; R^(14b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(14c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(14d), —F,—Cl, —Br, —I, —OH, —OR^(14d), —NO₂, —NH₂, —NHR^(14d), or —N(R^(14d))₂substituents; R^(14d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁵ is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(15a), —F, —Cl, —Br, —I, —OH,—OR^(15a), —NO₂, —NH₂, —NHR^(15a), or —N(R^(15a))₂ substituents; R^(15a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁶ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(16a);R^(16a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(16b), —NH₂,—NHR^(16b), —N(R^(16b))₂, or R^(16c) substituents; R^(16b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(16c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(16d), —F, —Cl, —Br, —I, —OH, —OR^(16d), —NO₂, —NH₂,—NHR^(16d), or —N(R^(16d))₂ substituents; R^(16d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁷ is C₂-alkenyl,C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, or R^(17a); R^(17a) isC₂-alkenyl, C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, OR^(17b), —NH₂, —NHR^(17b),—N(R^(17b))₂, or R^(17c) substituents; R^(17b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(17c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(17d), —F, —Cl, —Br, —I, —OH, —OR^(17d), —NO₂, —NH₂,—NHR^(17d), or —N(R^(17d))₂ substituents; R^(17d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁸ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(18a); R^(18a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(18b), —NH₂, —NHR^(18b),—N(R^(18b))₂, or R^(18c) substituents; R^(18b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(18c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(18d), —F, —Cl, —Br, —I, —OH, —OR^(18d), —NO₂, —NH₂,—NHR^(18d), or —N(R^(18d))₂ substituents; R^(18d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁹ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(19a); R^(19a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(19b), —NH₂, —NHR^(19b),—N(R^(19b))₂, or R^(19c) substituents; R^(19b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(19c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(19d), —F, —Cl, —Br, —I, —OH, —OR^(19d), —NO₂, —NH₂,—NHR^(19d), or —N(R^(19d))₂ substituents; R^(19d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁰ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(20a), —F, —Cl, —Br, —I, —OH, —OR^(20a), —NO₂, —NH₂,—NHR^(20a), or —N(R^(20a))₂ substituents; R^(20a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(21a); R^(21a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(21b), —NH₂, —NHR^(21b), —N(R^(21b))₂,or R^(21c) substituents; R^(21b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(21c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(21d), —F,—Cl, —Br, —I, —OH, —OR^(21d), —NO₂, —NH₂, —NHR^(21d), or —N(R^(21d))₂substituents; R^(21d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; X¹ is —O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—;R²² is R²³, —OH, —OR²³, —C(O)R²³, —C(O)OR²³, —C(O)OCH₂R²⁴, —R²⁵, or—CH₂R²⁵; R²³ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl,C₆-alkyl, or R^(23a); R^(23a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, C₆-alkyl, each of which is substituted with one or two orthree independently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH,—OR^(23b), —NH₂, —NHR^(23b), —N(R^(23b))₂, or R^(23c) substituents;R^(23b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl; R^(23c) is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(23d), —F, —Cl, —Br, —I, —OH,—OR^(23d), —NO₂, —NH₂, —NHR^(23d), or —N(R^(23d))₂ substituents; R^(23d)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁴ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(24a);R^(24a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl, each of which is substituted with one or two or threeindependently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(24b),—NH₂, —NHR^(24b), —N(R^(24b))₂, or R^(24c) substituents; R^(24b) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(24c)is phenyl, furanyl, imidazolyl, isothiazolyl, isoxazolyl,1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(24d), —F, —Cl, —Br, —I, —OH,—OR^(24d), —NO₂, —NH₂, —NHR^(24d), or —N(R^(24d))₂ substituents; R^(24d)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; andR²⁵ is phenyl, furanyl, imidazolyl, isothiazolyl, isoxazolyl,1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(25a), —F, —Cl, —Br, —I, —OH,—OR^(25a), —NO₂, —NH₂, —NHR^(25a), or —N(R^(25a))₂ substituents; R^(25a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl.

Variable moieties can combine with the parent molecular moieties of thecompounds of this invention to provide still even yet another embodimentof this invention, which embodiment pertains to compounds of thisinvention having formula (I), and salts, prodrugs, salts of prodrugs,and metabolites thereof, in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or—N(R⁷)₂; R² is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃,—O(CH₂CH═CH₂), or (2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸,—C(O)R⁸, or —C(O)OR⁸; R⁴ is hydrogen; R⁵ is hydrogen or R²⁰; R⁶ ishydrogen; R⁷ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl; R⁸ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl,C₆-alkyl, or R^(8a); R^(8a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl, each of which is substituted with one or two orthree independently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH,—OR^(8b), —NH₂, —NHR^(8b), or —N(R^(8b))₂ substituents; R²⁰ is phenyl,furanyl, pyrrolyl, or thiophenyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(20a), —F,—Cl, —Br, —I, —OH, —OR^(20a), —NO₂, —NH₂, —NHR^(20a), or —N(R^(20a))₂substituents; R^(20a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; X¹ is —O—, —S—, —S(O)—SO₂—, —NH—, or —NR²²—; andR²² is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, orR^(23a); R^(23a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl, each of which is substituted with one or two or threeindependently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(23b),—NH₂, —NHR^(23b), or —N(R^(23b))₂ substituents.

Variable moieties can also combine with the parent molecular moieties ofthe compounds of this invention to provide still even yet anotherembodiment of this invention, which embodiment pertains to compounds ofthis invention having formula (I), and salts, prodrugs, salts ofprodrugs, and metabolites thereof, in which R¹ is —OH, —OR⁷, —NH₂,—NHR⁷, or —N(R⁷)₂; R² is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃,—O(CH₂CH═CH₂), or (2,4-dimethoxyphenyl)methyl; R³ is hydrogen, C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁴ is hydrogen; R⁵is hydrogen, phenyl, furanyl, pyrrolyl, or thiophenyl; R⁶ is hydrogen;R⁷ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; X¹is —O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—; and R²² is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl.

R¹ is specifically embodied by —OH and —O(ethyl); R² is specificallyembodied by hydrogen and (2,4-dimethoxy-phenyl)methyl; R³ isspecifically embodied by methyl and ethyl; R⁴ is specifically embodiedby hydrogen; R⁵ is specifically embodied by hydrogen or phenyl; and R⁶is specifically embodied by hydrogen.

These specific embodiments can combine with the parent molecularmoieties of the compounds of this invention to provide still even yetanother embodiment of this invention, which embodiment pertains tocompounds of this invention having formula (I), and salts, prodrugs,salts of prodrugs, and metabolites thereof, in which R¹ is —OH or—O(ethyl); R² is hydrogen or (2,4-dimethoxyphenyl)methyl; R³ is methylor ethyl; R⁴ is hydrogen; R⁵ is hydrogen or phenyl; and R⁶ is hydrogen.

These specific embodiments can combine with the parent molecularmoieties of the compounds of this invention to provide still even yetanother embodiment of this invention, which embodiment pertains tocompounds of this invention having formula (I), and salts, prodrugs,salts of prodrugs, and metabolites thereof, which compounds are

-   6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid,-   4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid    6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid,-   4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid,-   6-(2,4-dimethoxybenzyl)-4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid, and-   4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylic    acid.

The compounds of this invention can have one or more than oneasymmetrically substituted carbon atoms in the R or S configuration, inwhich the terms “R” and “S” are as defined by the IUPAC 1974Recommendations for Section E, Fundamental Stereochemistry, Pure Appl.Chem. (1976) 45, 13-10. Compounds of this invention havingasymmetrically substituted carbon atoms enriched with one configurationover the other can be assigned the configuration which is present in thehigher amount, preferably about 85% to about 95% enrichment, morepreferably about 95% to about 99% enrichment, and still more preferablygreater than about 99% enrichment. Accordingly, compounds of thisinvention can exist as enantiomers, mixtures of enantiomers,diastereomers having relative stereochemistry, diastereomers havingabsolute stereochemistry, diastereomers having at least oneasymmetrically substituted carbon atom which is enriched in oneconfiguration and at least one asymmetrically substituted carbon atomwhich is not enriched, and mixtures comprising the foregoing.

The compounds of this invention can also contain carbon-carbon doublebonds or carbon-nitrogen double bonds in the Z or E configuration, inwhich the term “Z” means the two larger substituents are on the sameside of the carbon-carbon or carbon-nitrogen double bond, and the term“E” means the two larger substituents are on opposite sides of thecarbon-carbon or carbon-nitrogen double bond. The compounds of thisinvention can also exist as a mixture containing carbon-carbon doublebonds or carbon-nitrogen double bonds in both Z and E configurations.

Prodrugs of the compounds of this invention having formula (I) arederivatives of the same which can hydrolyze, oxidize, reduce, orotherwise react under in vivo or in an in vitro environment biologicalconditions. Compounds of this invention having formula (I) having an—OH, —NH—, —SH, or —CO₂H moiety can have attached therethrough aprodrug-forming moiety which is removed by metabolic processes torelease the compounds of this invention having formula (I) having thefreed —OH, —NH—, —SH, or —CO₂H moiety in vivo. Prodrugs are useful foradjusting such pharmacokinetic properties of the compounds of thisinvention having formula (I), or the salts thereof, as solubility,hydrophobicity, absorption in the gastrointestinal tract,bioavailability, tissue penetration, and rate of clearance. Accordingly,still even yet another embodiment of this invention pertains tocompounds of this invention having formula (I), or salts thereof, whichexist as prodrugs or to which are attached prodrug-forming moieties.

Compounds of this invention having formula (I), and prodrugs thereof,can exist as acid addition salts, basic addition salts, or zwitterions.Salts of the compounds of this invention having formula (I), andprodrugs thereof, can be prepared during their isolation or followingtheir purification. Acid addition salts of the compounds of thisinvention having formula (I), and prodrugs thereof, are those derivedfrom reacting the same and an acid. For example, the acetate, adipate,alginate, bicarbonate, citrate, aspartate, benzoate, benzenesulfonate,bisulfate, butyrate, camphorate, camphorsufonate, citrate, digluconate,formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptanoate,hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate,lactate, maleate, mesitylenesulfonate, methanesulfonate,naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate,persulfate, phosphate, picrate, propionate, succinate, tartrate,thiocyanate, trichloroacetate, trifluoroacetate, paratoluenesulfonate,and undecanoate salts of the compounds of this invention having formula(I), and prodrugs thereof, are meant to be included in this invention.Basic addition salts of the compounds of this invention having formula(I), and prodrugs thereof, can be prepared by reacting the same and abase such as the hydroxide, carbonate, bicarbonate, phosphate, hydrogenphosphate, or dihydrogen phosphate of cations such as calcium, iron,lithium, potassium, sodium, or magnesium.

Compounds of this invention having formula (I), and salts, prodrugs, andsalts of prodrugs thereof, can be administered with or without anexcipient. Excipients include encapsulating materials or formulationadditives such as absorption accelerators, antioxidants, binders,buffers, coating agents, coloring agents, diluents, disintegratingagents, emulsifiers, extenders, fillers, flavoring agents, humectants,lubricants, perfumes, preservatives, propellants, releasing agents,sterilizing agents, sweeteners, solubilizers, wetting agents, andmixtures thereof. Excipients for orally administered compounds of thisinvention having formula (I) and salts, prodrugs, and salts of prodrugsthereof, in solid dosage forms include agar, alginic acid, aluminumhydroxide, benzyl alcohol, benzyl benzoate, 1,3-butyleneglycol, castoroil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil,cottonseed oil, ethanol, ethyl acetate, ethyl carbonate, ethylcellulose, ethyl laureate, ethyl oleate, gelatin, germ oil, glucose,glycerol, groundnut oil, isopropanol, isotonic saline, lactose,magnesium hydroxide, magnesium stearate, malt, olive oil, peanut oil,potassium phosphate salts, potato starch, propylene glycol, Ringer'ssolution, talc, tragacanth, water, safflower oil, sesame oil, sodiumcarboxymethyl cellulose, sodium lauryl sulfate, sodium phosphate salts,soybean oil, sucrose, tetrahydrofurfuryl alcohol, and mixtures thereof.Excipients for ophthalmically and orally administered compounds of thisinvention having formula (I), and salts, prodrugs, and salts of prodrugsthereof, in liquid dosage forms include benzyl alcohol, benzyl benzoate,1,3-butyleneglycol, castor oil, corn oil, cottonseed oil, ethanol, ethylacetate, ethyl carbonate, fatty acid esters of sorbitan, germ oil,groundnut oil, glycerol, isopropanol, olive oil, polyethylene glycols,propylene glycol, sesame oil, tetrahydrofurfuryl alcohol, water, andmixtures thereof. Excipients for osmotically administered compounds ofthis invention having formula (I), and salts, prodrugs, and salts ofprodrugs thereof, include chlorofluoro-hydrocarbons, ethanol,isopropanol, water, and mixtures thereof. Excipients for parenterallyadministered compounds of this invention having formula (I), and salts,prodrugs, and salts of prodrugs thereof, include 1,3-butanediol, castoroil, corn oil, cottonseed oil, germ oil, groundnut oil, liposomes, oleicacid, olive oil, peanut oil, Ringer's solution, safflower oil, sesameoil, soybean oil, U.S.P. or isotonic sodium chloride solution, water,and mixtures thereof. Excipients for rectally and vaginally administeredcompounds of this invention having formula (I), and salts, prodrugs, andsalts of prodrugs thereof, include cocoa butter, polyethylene glycol,wax, and mixtures thereof.

Compounds of this invention having formula (I), and salts, prodrugs, andsalts of prodrugs thereof, can be administered orally, ophthalmically,osmotically, parenterally (subcutaneously, intramuscularly,intrasternally, intravenously), rectally, topically, transdermally, orvaginally. Orally administered compounds of this invention havingformula (I), and salts, prodrugs, and salts of prodrugs thereof, insolid dosage forms can be administered as capsules, dragees, granules,pills, powders, and tablets. Ophthalmically and orally administeredcompounds of this invention having formula (I), and salts, prodrugs, orsalts of 2.5 prodrugs thereof, in liquid dosage forms can beadministered as elixirs, emulsions, microemulsions, solutions,suspensions, and syrups. Osmotically and topically administeredcompounds of this invention having formula (I), and salts, prodrugs, orsalts of prodrugs thereof, can be administered as creams, gels,inhalants, lotions, ointments, pastes, powders, solutions, and sprays.Parenterally administered compounds of this invention having formula(I), and salts, prodrugs, and salts of prodrugs thereof, can beadministered as aqueous or oleaginous solutions or aqueous or oleaginoussuspensions which comprise crystalline, amorphous, or otherwiseinsoluble forms of the compounds of this invention having formula (I).Rectally and vaginally administered compounds of this invention havingformula (I), and salts, prodrugs, and salts of prodrugs thereof, can beadministered as creams, gels, lotions, ointments, and pastes.

The therapeutically acceptable amount of a compound of this inventionhaving formula (I), or a salt, prodrug, or salt of a prodrug thereof,depends on variables such as the recepient of treatment, the disorderbeing treated and the severity thereof, the composition containing thecompound, the time of administration, the route of administration, theduration of treatment, the potency of the compound, the rate ofclearance of the compound, and whether or not another drug isco-administered. The daily amount of a compound of this invention havingformula (I), or a salt, prodrug, or salt of a prodrug thereof,administered to a patient in a single dose or in divided doses, is fromabout 0.1 to about 200 mg/kg body weight, preferably from about 0.25 toabout 100 mg/kg body weight. Single dose compositions contain theseamounts of a compound of this invention having formula (I), or a salt,prodrug, or salt of a prodrug thereof, or combinations of submultiplesthereof.

To determine the antibacterial activity of the compounds of thisinvention having formula (I), twelve petri dishes, each containingsuccessive aqueous dilutions of representative compounds of thisinvention having formula (I) in sterilized Brain Heart Infusion agar(Difco 0418-01-5) (10 mL), were inoculated with 1:100 dilutions of therepresentative microorganisms in TABLE 1 using a Steers replicator block(or 1:10 dilutions for slow-growing Streptococcus strains), co-incubatedat 35-37° C. for 20-24 hours with a control plate having no compound,and inspected visually to provide the minimum inhibitory concentration(MIC), in μg/mL, by which is meant the lowest concentration of the testcompound of this invention having formula (I) which yielded no growth, aslight haze, or sparsely isolated colonies on the inoculums spot ascompared to growth in the control plate. TABLE 1 Microorganism CodeQuinolone Succeptable Streptococcus pneumoniae ATCC 6303 AAQuinolone-Resistant Streptococcus pneumoniae 7257 BB

TABLE 2 Example AA MIC BB MIC Ciprofloxacin 1 16 Norfloxacin 1 32Trovafloxacin 0.06 4 Linezolid 2 0.5

The antibacterial activity of the representative compounds of thisinvention having formula (I) was superior to the control containing nocompound and in the range of greater than about 64 μg/mL to greater thanabout 64 μg/mL against AA and about 32 μg/mL to greater than about 64μg/mL μg/mL against BB. These data demonstrate the utility of thecompounds of this invention having formula (I) as antibacterials.

Bacterial protein synthesis inhibitory activity of representativecompounds of this invention having formula (I) and thecommercially-available antibacterials in TABLE 2 was determined bytranslation assays using the firefly luciferase reporter systemdescribed by Murray et al., (2001), “Staphylococcus aureus Cell ExtractTranscription-Translation Assay: Firefly Luciferase Reporter System forEvaluating Protein Translation Inhibitors,” Antimicrob. AgentsChemother. 45(6): 1900-1904, but replacing the Staphylococcus aureus S30extract described therein with S30 Streptococcus pneumoniae extract fromquinolone-succeptable Streptococcus pneumoniae ATCC 46919, and replacingplasmid coding for the luciferase gene with mRNA (encoding produced byin an in vitro environment transcription from the plasmid pAS10rbs3)which encoded the luciferase gene with an upstream Streptococcuspneumoniae promoter and Shine-Dalgarno site.

The IC₅₀'s of the representative compounds of this invention havingformula (I), defined as concentrations of the same which caused 50%inhibition of bacterial protein synthesis, were in the range of about 8μM to about 80 μM.

The IC₅₀'s of the commercially-available quinolones tested were greaterthan about 100 μM compared to the IC₅₀ of linezolid which is about 3 μM.

These data demonstrate that the commercially-available quinolones whichwere tested do not inhibit bacterial protein synthesis in Streptococcuspneumoniae, even at high concentrations, that the utility of thecompounds of this invention having formula (I) as antibacterials is due,at least in part, to their ability to inhibit bacterial proteinsynthesis, and therefore bacterial growth, and that the inhibition ofbacterial protein synthesis by the compounds of this invention havingformula (I) would be comparable to the inhibition of bacterial proteinsynthesis provided by linezolid.

Therefore, while not being limited by theory, the compounds of thisinvention having formula (I) would be expected to function by amechanism more similar to linezolid (which inhibits bacterial proteinsynthesis) than quinolones (which inhibit the enzyme DNA gyrase).

Because the representative compounds of this invention having formula(I) inhibit the growth of quinolone resistant bacteria at least as wellas the growth of quinolone susceptible bacteria, and because theyfunction by a mechanism which differs from quinolones, the compounds ofthis invention having formula (I), and the salts, prodrugs, salts ofprodrugs, and metabolites thereof, would be expected to be useful notonly for treating bacterial infections but also for treating bacterialinfections for which quinolones would be ineffective or only partiallyeffective.

Metabolites of the compounds of this invention having formula (I),produced by in an in vitro environment or in vivo metabolic processes,can also be useful as antibacterials. Once identified, these metabolitescan also be synthesized and evaluated for utility as antibacterials.

Compounds of this invention having formula (I), and salts, prodrugs, andsalts of prodrugs, can be prepared by chemical processes, examples ofwhich chemical processes and intermediates used in the processes areshown in the following schemes. It is meant to be understood that theorder of the steps in the processes can be varied, that differentintermediates, reagents, solvents, and reaction conditions can besubstituted for those specifically mentioned, and that vulnerablemoieties can be protected and deprotected, as needed, during theprocesses.

Compounds having formula (1), in which X¹ is —Br or —Cl, can beconverted to compounds having formula (2) by reacting the former and acompound having formula (i)

in which M is sodium or potassium.

This step is typically conducted at about 0° C. to 25° C., over about 1to 24 hours, in solvents such as dichloromethane, chloroform, THF, andmixtures thereof.

Compounds having formula (2) may be converted to compounds havingformula (3) by reacting the former, triethyl orthoformate, and aceticanhydride. The reaction is typically conducted from about 1 to 6 hours,at about

80° C. to 140° C., in acetic anhydride.

Compounds having formula (3) may be converted to compounds havingformula (4) by reacting the former, a first base and compounds havingformula (ii)R²—NH₂  (ii),

in which R² is a nitrogen protecting group. Nitrogen protecting groupsinclude allyloxy, 2,4-dimethoxybenzyl, 2-cyanoethyl, 4-methoxybenzyl,trimethylsilyl, tert-butyl, and triphenylmethyl. First bases includepotassium carbonate, sodium carbonate, sodium hydride, and potassiumhydride. The reaction is typically conducted from about ½ hour to 7days, at about 0° C. to 100° C., in solvents such as dichloromethane,acetonitrile, THF, and mixtures thereof.

Compounds having formula (4) may be converted to compounds havingformula (4a) by reacting the former and lithium hydroxide. Compoundshaving formula (4a) may be converted to compounds having formula (5) byreacting the former, diisopropylethylamine, and compounds having formula(iii)

This step is typically conducted at about 24° C. to 40° C., over about24 hours to 5 days, in solvents such as acetonitrileN,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran, and mixturesthereof.

Compounds having formula (5) may be converted to compounds havingformula (I) by reacting the former and the first base.

The —CO₂H moieties of the compounds of the invention can be reacted withammonia or an amine having formula —NHR⁹, or —N(R⁹)₂ and a dehydratingagent, with or without the first base, and with or without a promoter.Examples of dehydrating agents include carbonyldiimidazole,1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride anddicyclohexylcarbodiimide. Examples of promoters include1-hydroxybenzotriazole and 4-(N,N-dimethylamino)-pyridine. The reactionsare typically conducted at about 0° C. to about 35° C., for about 1 hourto about 24 hours, in solvents such as N,N-dimethylformamide,tetrahydrofuran, dioxane, water, ethyl acetate, and acetonitrile.

EXAMPLE 1A ethyl(2E/Z)-2-((2,6-dichloro-5-fluoropyridin-3-yl)carbonyl)-3-(ethoxy)prop-2-enoate

Ethyl 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropanoate (40 g) andtriethyl orthoformate (26.1 mL) in acetic anhydride (100 mL) werestirred at 85° C. for 6.5 hours, cooled, and concentrated. Theconcentrate was crystallized from hexanes with a small amount of diethylether and dichloromethane.

EXAMPLE 1B ethyl7-chloro-1-(2,4-dimethoxybenzyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylicacid

Example 1A (48 g) in dichloromethane (500 mL) at 0° C. was treated with2,4-dimethoxybenzylamine (22 mL), stirred for 1 hour, warmed to ambienttemperature, stirred for 1 hour, and concentrated. The concentrate wasdissolved in acetonitrile (250 mL), treated with potassium carbonate (41g), heated at 75° C. for 18 hours, cooled, diluted with ethyl acetate,washed with water, 10% citric acid, water, and brine, dried overanhydrous magnesium sulfate, filtered, and concentrated. The concentratewas recrystallized from ethyl acetate/hexanes.

EXAMPLE 1C ethyl1-(2,4-dimethoxybenzyl)-6-fluoro-7-((2-hydroxy-2-phenylethyl)(methyl)amino)-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate

EXAMPLE 1B (2 g), DL-α-(methylamino-methyl)benzyl alcohol (934 mg) andtriethylamine (1.98 mL) in acetonitrile (47.5 mL) at 25° C. was stirredfor 18 hours, treated with water, adjusted to pH 3.5, and filtered.

EXAMPLE 1D1-(2,4-dimethoxybenzyl)-6-fluoro-7-((2-hydroxy-2-phenylethyl)(methyl)amino)-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylicacid

EXAMPLE 1C (2.66 g) in isopropanol (200 mL) was treated with 1M NaOH (14mL), stirred for 24 hours, treated with water (400 mL), adjusted to pH3.5 with 1M HCl, and filtered.

EXAMPLE 1E6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 1D (1 g) in DMF (40 mL) at 0° C. was treated with 60% oilysodium hydride (189 mg), stirred for 30 minutes, heated at 110° C. for 3days, cooled, treated with water (150 mL), adjusted to pH 3.5 with 1MHCl, and filtered. The filtrant was flash chromatographed on silica gelwith 0-2% methanol/dichloromethane.

EXAMPLE 1F4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 1E (775 mg) in trifluoroacetic acid (30 mL) was stirred at 25°C. for 18 hours, concentrated, and flash chromatographed on silica gelwith 0-10% methanol/dichloromethane. Relevant fractions were combined,concentrated, and recrystallized twice from dimethylsulfoxide, andtriturated with acetone. ¹H NMR (300 MHz, DMSO-d₆) δ 8.42 (m, 1H), 7.57(m, 1H), 7.46 (m, 5H), 5.31 (dd, J=8.48 Hz, 3.39 Hz, 1H), 3.83 (m, 2H),3.27 (m, 3H).

EXAMPLE 2A ethyl1-(2,4-dimethoxybenzyl)-6-fluoro-7-((2-hydroxyethyl)-(methyl)amino)-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate

EXAMPLE 1B (2 g), N-methylaminoethanol (572 μL), and triethylamine (2mL) in acetonitrile (50 mL) at 25° C. was stirred for 18 hours andfiltered.

EXAMPLE 2B1-(2,4-dimethoxybenzyl)-6-fluoro-7-((2-hydroxyethyl)-(methyl)amino)-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylicacid

EXAMPLE 2A (2.09 g) and 1M NaOH (14 mL) in ethanol (100 mL) was stirredfor 24 hours, treated with water (300 mL), adjusted to pH 3.5 with 1MHCl, and filtered.

EXAMPLE 2C6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 2B (1 g) in N,N-dimethylformamide (45 mL) at 25° C. was treatedwith 60% oily sodium hydride (195 mg), stirred for 4 hours, heated at110° C. for 2 days and cooled, treated with water (150 mL), adjusted topH 3.5 with 1M HCl, and filtered. The filtrant was flash chromatographedon silica gel with 0-3% methanol/dichloromethane.

EXAMPLE 2D4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 2C (284 mg) in trifluoroacetic acid (20 mL) at 25° C. wasstirred for 18 hours, concentrated, and triturated with acetone thenmethanol. ¹H NMR (300 MHz, DMSO-d₆) δ 15.87 (m, 1H), 13.08 (d, J=5.88Hz, 1H), 8.39 (d, J=6.99 Hz, 1H), 7.43 (m, 1H), 4.26 (dd, J=9.19 Hz,4.41 Hz, 2H), 3.66 (dd, J=9.56 Hz, 2.94 Hz, 2H), 3.23 (m, 3H).

EXAMPLE 3A ethyl1-(2,4-dimethoxybenzyl)-7-(ethyl(2-hydroxyethyl)amino)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate

EXAMPLE 1B (2 g), 2-(ethylamino)ethanol (556 μL) and triethylamine (1.98mL) in acetonitrile (47.5 mL) at 25° C. was stirred for 18 hours,treated with 2-(ethylamino)ethanol (556 μL), heated at 55-75° C. for 4days, cooled, and filtered.

EXAMPLE 3B1-(2,4-dimethoxybenzyl)-7-(ethyl(2-hydroxyethyl)amino)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylicacid

EXAMPLE 3A (1.96 g) in ethanol (100 mL) was treated with 1M sodiumhydroxide (14 mL), stirred for 24 hours, treated with water (300 mL),adjusted to pH 3.5 with 1M hydrochloric acid, and filtered.

EXAMPLE 3C6-(2,4-dimethoxybenzyl)-4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 3B (1.14 g) in N,N-dimethylformamide (45 mL) at 25° C. wastreated with 60% oily sodium hydride (215 mg), stirred for 4 hours,heated at 100° C. for 2 days, cooled to 25° C., treated with more 60%oily sodium hydride (100 mg), stirred for 4 hours, heated at 100° C. for2 days, cooled to 25° C., treated with water, adjusted to pH 3.5 with 1MHCl, and filtered. The filtrant was flash chromatographed on silica gelwith 0-4% methanol/dichloromethane.

EXAMPLE 3D4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid

EXAMPLE 3C (498 mg) in trifluoroacetic acid (20 mL) at 25° C. wasstirred for 18 hours, concentrated and triturated with acetone thenmethanol. ¹H NMR (300 MHz, DMSO-d₆) δ 15.88 (s, 1H), 13.07 (d, J=4.78Hz, 1H), 8.37 (d, J=6.62 Hz, 1H), 7.45 (s, 1H), 4.26 (dd, J=9.19 Hz,4.41 Hz, 2H), 3.76 (q, J=6.99 Hz, 2H), 3.66 (dd, J=9.19 Hz, 4.78 Hz,2H), 1.20 (t, J=6.99 Hz, 3H).

These examples are merely illustrative of this invention and are notintended to limit the same to the specifically embodied compounds andprocesses. Variations and changes which are obvious to one skilled inthe art are intended to be within the scope of this invention as definedin the appended claims.

1. A compound having formula (I)

or a salt thereof, in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or —N(R⁷)₂; R²is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃, —O(CH₂CH═CH₂), or(2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸, —C(O)R⁸, —C(O)OR⁸, R⁹,—C(O)OCH₂R⁹, or R¹⁰; R⁴ is hydrogen, R¹¹, —C(O)R¹¹, R¹², R¹³, R¹⁴, orR¹⁵; R⁵ is hydrogen, R¹⁶, —C(O)R¹⁶, R¹⁷, R¹⁸, R¹⁹, or R²⁰; R⁶ ishydrogen, R²¹, —OH, —OR²¹, —NH₂, —NHR²¹, —N(R²¹)₂; R⁷ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁸ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(8a); R^(8a) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(8b), —NH₂, —NHR^(8b),—N(R^(8b))₂, or R^(8c) substituents; R^(8b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(8c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(8d), —F, —Cl, —Br, —I, —OH, —OR^(8d), —NO₂, —NH₂, —NHR^(8d),or —N(R^(8d))₂ substituents; R^(8d) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁹ is phenyl which is unfused or fusedwith benzene, cyclopentane, cyclopentene, cyclohexane, or cyclohexene,in which each ring is independently unsubstituted or substituted withone or two or three independently selected R^(9a), —F, —Cl, —Br, —I,—OH, —OR^(9a), —NO₂, —NH₂, —NHR^(9a), or —N(R^(9a))₂ substituents;R^(9a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl;R¹⁰ is furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(10a), —F, —Cl, —Br, —I, —OH, —OR^(10a), —NO₂, —NH₂,—NHR^(10a), or —N(R^(10a))₂ substituents; R^(10a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(11a); R^(11a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b), —NH₂, —NHR^(11b), —N(R^(11b))₂,or R^(11c) substituents; R^(11b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(11c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(11d), —F,—Cl, —Br, —I, —OH, —OR^(11d), —NO₂, —NH₂, —NHR^(11d), or —N(R^(11d))₂substituents; R^(11d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹² is C₂-alkenyl, C₃-alkenyl, C₄-alkenyl,C₅-alkenyl, C₆-alkenyl, or R^(12a); R^(12a) is C₂-alkenyl, C₃-alkenyl,C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(12b), —NH₂, —NHR^(12b), —N(R^(12b))₂, or R^(12c)substituents; R^(12b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(12c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(12d), —F,—Cl, —Br, —I, —OH, —OR^(12d), —NO₂, —NH₂, —NHR^(12d), or —N(R^(12d))₂substituents; R^(12d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹³ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(13a); R^(13a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(13b), —NH₂, —NHR^(13b)—N(R^(13b))₂, or R^(13c)substituents; R^(13b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(13c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(13d), —F,—Cl, —Br, —I, —OH, —OR^(13d), —NO₂, —NH₂, —NHR^(13d), or —N(R^(13d))₂substituents; R^(13d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁴ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(14a); R^(14a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(14b), —NH₂, —NHR^(14b), —N(R^(14b))₂, or R^(14c)substituents; R^(14b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(14c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(14d), —F,—Cl, —Br, —I, —OH, —OR^(14d), —NO₂, —NH₂, —NHR^(14d), or —N(R^(14d))₂substituents; R^(14d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁵ is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unfused or fused with benzene, furan,imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, oxazole, pyrazine,pyrazole, pyridazine, pyridine, pyrrole, thiazole, or thiophene, inwhich each ring is independently unsubstituted or substituted with oneor two or three independently selected R^(15a), —F, —Cl, —Br, —I, —OH,—OR^(15a), —NO₂, —NH₂, —NHR^(15a), or —N(R^(15a))₂ substituents; R^(15a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁶ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(16a);R^(16a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b), —NH₂,—NHR^(11b), —N(R^(11b))₂, or R^(16c) substituents; R^(16b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(16c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(16d), —F, —Cl, —Br, —I, —OH, —OR^(16d), —NO₂, —NH₂,—NHR^(16d), or —N(R^(16d))₂ substituents; R^(16d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁷ is C₂-alkenyl,C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, or R^(17a); R^(17a) isC₂-alkenyl, C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(17b), —NH₂, —NHR^(17b),—N(R^(17b))₂, or R^(17c) substituents; R^(17b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(17c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(17d), —F, —Cl, —Br, —I, —OH, —OR^(17d), —NO₂, —NH₂,—NHR^(17d), or —N(R^(17d) d)₂ substituents; R^(17d) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁸ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(18a); R^(18a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(18b), —NH₂, —NHR^(18b),—N(R^(18b))₂, or R^(18c) substituents; R^(18b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(18c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(18d), —F, —Cl, —Br, —I, —OH, —OR^(18d), —NO₂, —NH₂,—NHR^(18d), or —N(R^(18d))₂ substituents; R^(18d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁹ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(19a); R^(19a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(19b), —NH₂, —NHR^(19b),—N(R^(19b))₂, or R^(19c) substituents; R^(19b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(19c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(19d), —F, —Cl, —Br, —I, —OH, —OR^(19d), —NO₂, —NH₂,—NHR^(19d), or —N(R^(19d))₂ substituents; R^(19d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁰ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(20a), —F, —Cl, —Br, —I, —OH, —OR^(20a), —NO₂, —NH₂,—NHR^(20a), or —N(R^(20a))₂ substituents; R^(20a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²¹ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(21a); R^(21a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(21b), —NH₂, —NHR^(21b), —N(R^(21b))₂,or R^(21c) substituents; R^(21b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(21c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unfused or fused withbenzene, furan, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole,oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrrole, thiazole, orthiophene, in which each ring is independently unsubstituted orsubstituted with one or two or three independently selected R^(21d), —F,—Cl, —Br, —I, —OH, —OR^(21d), —NO₂, —NH₂, —NHR^(21d), or —N(R^(21d))₂substituents; R^(21d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; X¹ is —O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—;R²² is R²³, —OH, —OR²³, —C(O)R²³, —C(O)OR²³, —C(O)OCH₂R²⁴, —R²⁵, or—CH₂R²⁵; R²³ is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl,C₆-alkyl, or R^(23a); R^(23a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, C₆-alkyl, each of which is substituted with one or two orthree independently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH,—OR^(23b), —NH₂, —NHR^(23b), —N(R^(23b))₂, or R^(23c) substituents;R^(23b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl; R^(23c) is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unfused or fused with benzene, furan,imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, oxazole, pyrazine,pyrazole, pyridazine, pyridine, pyrrole, thiazole, or thiophene, inwhich each ring is independently unsubstituted or substituted with oneor two or three independently selected R^(23d), —F, —Cl, —Br, —I, —OH,—OR^(23d), —NO₂, —NH₂, —NHR^(23d), or —N(R^(23d))₂ substituents; R^(23d)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁴ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(24a);R^(24a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(24b), —NH₂,—NHR^(24b), —N(R^(24b))₂, or R^(24c) substituents; R^(24b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(24c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunfused or fused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(24d), —F, —Cl, —Br, —I, —OH, —OR^(24d), —NO₂, —NH₂,—NHR^(24d), or —N(R^(24d))₂ substituents; R^(24d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; and R²⁵ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which is unfused orfused with benzene, furan, imidazole, isothiazole, isoxazole,1,2,3-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine,pyrrole, thiazole, or thiophene, in which each ring is independentlyunsubstituted or substituted with one or two or three independentlyselected R^(25a), —F, —Cl, —Br, —I, —OH, —OR^(25a)—NO₂, —NH₂,—NHR^(25a), or —N(R^(25a))₂ substituents; R^(25a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl.
 2. A compound of claim 1having formula (I), or a salt thereof, in which R¹ is —OH, —OR⁷, —NH₂,—NHR⁷, or —N(R⁷)₂; R² is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃,—O(CH₂CH═CH₂), or (2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸,—C(O)R⁸, —C(O)OR⁸, R⁹, —C(O)OCH₂R⁹, or R¹⁰; R⁴ is hydrogen, R¹¹,—C(O)R¹¹, R¹², R¹³, R¹⁴, R¹⁵; R⁵ is hydrogen, R¹⁶, —C(O)R¹⁶, R¹⁷, R¹⁸,R¹⁹, or R²⁰; R⁶ is hydrogen, R²¹, —OH, —OR²¹, —NH₂, —NHR²¹, —N(R²¹)₂; R⁷is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁸ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(8a);R^(8a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(8b), —NH₂,—NHR^(8b), —N(R^(8b))₂, or R^(8c) substituents; R^(8b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(8c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(8d), —F, —Cl, —Br, —I, —OH, —OR^(8d), —NO₂, —NH₂, —NHR^(8d),or —N(R^(8d))₂ substituents; R^(8d) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁹ is phenyl which is unsubstituted orsubstituted with one or two or three independently selected R^(9a), —F,—Cl, —Br, —I, —OH, —OR^(9a), —NO₂, —NH₂, —NHR^(9a), or —N(R^(9a))₂substituents; R^(9a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁰ is furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(10a), —F, —Cl, —Br, —I, —OH,—OR^(10a), —NO₂, —NH₂, —NHR^(10a), or —N(R^(10a))₂ substituents; R^(10a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹¹ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(11a);R^(11a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl,each of which is substituted with one or two or three independentlyselected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(11b), —NH₂,—NHR^(11b), —N(R^(11b))₂, or R^(11c) substituents; R^(11b) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(11c) is phenyl,furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl,oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl,thiazolyl, thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(11d), —F, —Cl, —Br, —I, —OH, —OR^(11d), —NO₂, —NH₂,—NHR^(11d), or —N(R^(11d))₂ substituents; R^(11d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹² is C₂-alkenyl,C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, or R^(12a); R^(12a) isC₂-alkenyl, C₃-alkenyl, C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(12b), —NH₂, —NHR^(12b),—N(R^(12b))₂, or R^(12c) substituents; R^(12b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(12c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(12d), —F, —Cl, —Br, —I, —OH, —OR^(12d) —NO₂, —NH₂,—NHR^(12d), or —N(R^(12d))₂ substituents; R^(12d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹³ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(13a); R^(13a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(13b), —NH₂, NHR^(13b),—N(R^(13b))₂, or R^(13c) substituents; R^(13b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(13c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(13d), —F, —Cl, —Br, —I, —OH, —OR^(13d), —NO₂, —NH₂,—NHR^(13d), or —N(R^(13d))₂ substituents; R^(13d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁴ is C₂-alkynyl,C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkenyl, or R^(14a); R^(14a) isC₂-alkynyl, C₃-alkynyl, C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(14b), —NH₂, —NHR^(14b),—N(R^(14b))₂, or R^(14c) substituents; R^(14b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(14c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(14d), —F, —Cl, —Br, —I, —OH, —OR^(14d), —NO₂, —NH₂,—NHR^(14d), or —N(R^(14d))₂ substituents; R^(14d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁵ is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(15a), —F, —Cl, —Br, —I, —OH, —OR^(15a)—NO₂, —NH₂,—NHR^(15a), or —N(R^(15a))₂ substituents; R^(15a) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R¹⁶ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(16a); R^(16a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(16b), —NH₂, —NHR^(16b), —N(R^(16b))₂,or R^(16c) substituents; R^(16b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(16c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(16d), —F,—Cl, —Br, —I, —OH, —OR^(16d), —NO₂, —NH₂, —NHR^(16d), or —N(R^(16d))₂substituents; R^(16d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁷ is C₂-alkenyl, C₃-alkenyl, C₄-alkenyl,C₅-alkenyl, C₆-alkenyl, or R^(17a); R^(17a) is C₂-alkenyl, C₃-alkenyl,C₄-alkenyl, C₅-alkenyl, C₆-alkenyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(17b), —NH₂, —NHR^(17b), —N(R^(17b))₂, or R^(17c)substituents; R^(17c) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(17c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(17d), —F,—Cl, —Br, —I, —OH, —OR^(17d), —NO₂, —NH₂, —NHR^(17d), or —N(R^(17d))₂substituents; R^(17d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁸ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(18a); R^(18a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(18b), —NH₂, —NHR^(18b), —N(R^(18b))₂, or R^(18c)substituents; R^(18b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(18c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(18d), —F,—Cl, —Br, —I, —OH, —OR^(18d), —NO₂, —NH₂, —NHR^(18d), or —N(R^(18d))₂substituents; R^(18d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R¹⁹ is C₂-alkynyl, C₃-alkynyl, C₄-alkynyl,C₅-alkynyl, C₆-alkenyl, or R^(19a); R^(19a) is C₂-alkynyl, C₃-alkynyl,C₄-alkynyl, C₅-alkynyl, C₆-alkynyl, each of which is substituted withone or two or three independently selected —F, —Cl, —Br, —I, —CF₃,—CF₂CF₃, —OH, —OR^(19b), —NH₂, —NHR^(19b)—N(R^(19b))₂, or R^(19c)substituents; R^(19b) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R^(19c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(19d), —F,—Cl, —Br, —I, —OH, —OR^(19d), —NO₂, —NH₂, —NHR^(19d), or —N(R^(19d))₂substituents; R^(19d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; R²⁰ is phenyl, furanyl, imidazolyl, isothiazolyl,isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(20a), —F, —Cl, —Br, —I, —OH,—OR^(20a), —NO₂, —NH₂, —NHR^(20a), or —N(R^(20a))₂ substituents; R^(20a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²¹ isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(21a);R^(21a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, orC₆-alkyl, each of which is substituted with one or two or threeindependently selected —F, —Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(21b),—NH₂, —NHR^(21b), —N(R^(21b))₂, or R^(21c) substituents; R^(21b) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(21c)is phenyl, furanyl, imidazolyl, isothiazolyl, isoxazolyl,1,2,3-oxadiazoyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridinyl, pyrrolyl, thiazolyl, thiophenyl, triazinyl, or1,2,3-triazolyl, each of which is unsubstituted or substituted with oneor two or three independently selected R^(21d), —F, —Cl, —Br, —I, —OH,—OR^(21d), —NO₂, —NH₂, —NHR^(21d), or —N(R^(21d))₂ substituents; R^(21d)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; X¹ is—O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—; R²² is R²³, —OH, —OR²³,—C(O)R²³, —C(O)OR²³, —C(O)OCH₂R²⁴, —R²⁵, or —CH₂R²⁵; R²³ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(23a); R^(23a) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(23b), —NH₂, —NHR^(23b),—N(R^(23b))₂, or R^(23c) substituents; R^(23b) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(23c) is phenyl, furanyl,imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl,thiophenyl, triazinyl, or 1,2,3-triazolyl, each of which isunsubstituted or substituted with one or two or three independentlyselected R^(23d), —F, —Cl, —Br, —I, —OH, —OR^(23d), —NO₂, —NH₂,—NHR^(23d), or —N(R^(23d))₂ substituents; R^(23d) is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R²⁴ is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(24a); R^(24a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(24b), —NH₂, —NHR^(24b), —N(R^(24b))₂,or R^(24c) substituents; R^(24b) is C₁-alkyl, C₂-alkyl, C₃-alkyl,C₄-alkyl, C₅-alkyl, or C₆-alkyl; R^(24c) is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(24d), —F,—Cl, —Br, —I, —OH, —OR^(24d), —NO₂, —NH₂, —NHR^(24d), or —N(R^(24d))₂substituents; R^(24d) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl; and R²⁵ is phenyl, furanyl, imidazolyl,isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, oxazolyl, pyrazinyl,pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiazolyl, thiophenyl,triazinyl, or 1,2,3-triazolyl, each of which is unsubstituted orsubstituted with one or two or three independently selected R^(25a), —F,—Cl, —Br, —I, —OH, —OR^(25a) —NO₂, —NH₂, —NHR^(25a), or —N(R^(25a))₂substituents; R^(25a) is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl,C₅-alkyl, or C₆-alkyl.
 3. A compound of claim 2 having formula (I), or asalt thereof, in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or —N(R⁷)₂; R² ishydrogen or R^(P), in which R^(P) is —C(CH₃)₃, —O(CH₂CH═CH₂), or(2,4-dimethoxyphenyl)methyl; R³ is hydrogen, R⁸, —C(O)R⁸, or —C(O)OR⁸;R⁴ is hydrogen; R⁵ is hydrogen or R²⁰; R⁶ is hydrogen; R⁷ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁸ is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(8a); R^(8a) isC₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl, each ofwhich is substituted with one or two or three independently selected —F,—Cl, —Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(8b), —NH₂, —NHR^(8b), or—N(R^(8b))₂ substituents; R²⁰ is phenyl, furanyl, pyrrolyl, orthiophenyl, each of which is unsubstituted or substituted with one ortwo or three independently selected R^(20a), —F, —Cl, —Br, —I, —OH,—OR^(20a), —NO₂, —NH₂, —NHR^(20a), or —N(R^(20a))₂ substituents; R^(20a)is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; X¹ is—O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—; and R²² is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, C₆-alkyl, or R^(23a); R^(23a) is C₁-alkyl,C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl, each of which issubstituted with one or two or three independently selected —F, —Cl,—Br, —I, —CF₃, —CF₂CF₃, —OH, —OR^(23b), —NH₂, —NHR^(23b), or—N(R^(23b))₂ substituents.
 4. A compound of claim 3 having formula (I),or a salt thereof, in which R¹ is —OH, —OR⁷, —NH₂, —NHR⁷, or —N(R⁷)₂; R²is hydrogen or R^(P), in which R^(P) is —C(CH₃)₃, —O(CH₂CH═CH₂), or(2,4-dimethoxyphenyl)methyl; R³ is hydrogen, C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; R⁴ is hydrogen; R⁵ ishydrogen, phenyl, furanyl, pyrrolyl, or thiophenyl; R⁶ is hydrogen; R⁷is C₁-alkyl, C₂-alkyl, C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl; X¹ is—O—, —S—, —S(O)—, —SO₂—, —NH—, or —NR²²—; and R²² is C₁-alkyl, C₂-alkyl,C₃-alkyl, C₄-alkyl, C₅-alkyl, or C₆-alkyl.
 5. A compound of claim 4having formula (I), or a salt thereof, in which R¹ is —OH or —O(ethyl);R² is hydrogen or (2,4-dimethoxyphenyl)methyl; R³ is methyl or ethyl; R⁴is hydrogen; R⁵ is hydrogen or phenyl; and R⁶ is hydrogen.
 6. A compoundof claim 5 having formula (I), or a salt thereof, which is6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid,4-methyl-9-oxo-2-phenyl-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid6-(2,4-dimethoxybenzyl)-4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid,4-methyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid,6-(2,4-dimethoxybenzyl)-4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid, or4-ethyl-9-oxo-3,4,6,9-tetrahydro-2H-[1,4]oxazino[3,2-b][1,8]naphthyridine-8-carboxylicacid.
 7. A composition for treating bacterial infections in a fish or amammal, the compositions comprising a therapeutically effective amountof a compound having formula (I), or a salt thereof, and an excipient.8. A method for treating bacterial infections in a fish or a mammal, themethod comprising administering thereto a therapeutically effectiveamount of compound having formula (I), or a salt thereof.